The invention relates to a method of the inhibition of unwanted hair growth in mammals.
A main function of mammalian hair is to provide environmental protection. However, that function has largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory creams or lotions, waxing, plucking, and therapeutic antiandrogens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair. Finally, antiandrogens--which have been used to treat female hirsutism--can have unwanted side effects.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Breuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007; Ahluwalia et al., U.S. Pat. No. 5,096,911; Shander et al., U.S. Pat. No. 5,132,293; and Shander et al., U.S. Pat. No. 5,143,925.
Angiogenesis, the development of new blood vessels, is the cumulative effect of many biochemical processes and occurs mainly during embryonic growth, wound healing, and the cyclical development of the uterine endometrium. Angiogenesis also plays a role in diabetic retinopathy, atherosclerosis, and tumor growth. Angiogenesis involves the degradation of both the parent vessel basement membrane and the interstitial matrix to provide a passage for the new vessel; migration of endothelial cells toward an angiogenic stimulus; formation of a lumen and the initiation of blood flow. These processes are under the control of growth factors, cytokines, peptides, immunomodulators, as well as other factors that may act as direct stimulants of angiogenesis or as indirect stimulants by attracting inflammatory factors.
There are at least seven major pathways thought to contribute to angiogenesis.
The first pathway involves heparin sulfate proteoglycans (HSPG). HSPG binds basic fibroblast growth factor (bFGF), and stimulates angiogenesis in the presence of copper ions. HSPG is formed from heparin by the enzyme sulfotransferase.
The second pathway involves histamine, which may stimulate angiogenesis after binding to specific histamine receptors. Histamine is formed from the amino acid histidine by the enzyme histidine decarboxylase (HDC). This synthetic reaction takes place in mast cells, and histamine is released from mast cells upon their degranulation.
The third pathway involves angiotensin II, which stimulates angiogenesis after binding to angiotensin II receptors. Angiotensin II is formed from angiotensin I by angiotensin converting enzyme (ACE).
The fourth pathway involves prostaglandin E1, which stimulates angiogenesis. Prostaglandin E1 synthesis is catalyzed by the enzyme prostaglandin synthase.
The fifth pathway involves Substance P, an endogenous molecule that functions as a neurotransmitter and in the regulation of inflammation. Substance P also possesses angiogenic properties by acting through the neurokinin 1 receptor (NK1).
The sixth pathway involves platelet activating factor (PAF), an endogenous protein that binds to a specific receptor and stimulates chemotaxis and leukocyte infiltration, which can lead to the stimulation of angiogenesis.
The seventh pathway involves the arachidonic acid metabolite 12(R)-HETrE, which is angiogenic through its effects on capillary permeability, neutrophil chemotaxis, vasodilation, and endothelial cell mitogenesis. The metabolite 12(R)-HETrE is formed from 5HETE by the enzyme cytochrome P450 reductase.